Objective:To investigate whether blood-brain barrier(BBB)served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points(HTWP)in traumatic brain injury(TBI)and the potential molec...Objective:To investigate whether blood-brain barrier(BBB)served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points(HTWP)in traumatic brain injury(TBI)and the potential molecular signaling pathways.Methods:Adult male Sprague-Dawley rats were assigned to the shamoperated(sham),TBI,and bloodletting puncture(bloodletting)groups(n=24 per group)using a randomized number table.The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days.The neurological function and cerebral edema were evaluated by modified neurological severity score(mNSS),cerebral water content,magnetic resonance imaging and hematoxylin and eosin staining.Cerebral blood flow was measured by laser speckles.The protein levels of aquaporin 4(AQP4),matrix metalloproteinases 9(MMP9)and mitogen-activated protein kinase pathway(MAPK)signaling were detected by immunofluorescence staining and Western blot.Results:Compared with TBI group,bloodletting puncture improved neurological function at 24 and 48 h,alleviated cerebral edema at 48 h,and reduced the permeability of BBB induced by TBI(all P<0.05).The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture(P<0.05 or P<0.01).In addition,the extracellular signal-regulated kinase(ERK)and p38 signaling pathways were inhibited by bloodletting puncture(P<0.05).Conclusions:Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways.Therefore,bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.展开更多
目的:制备肿瘤微环境响应释放的靶向二硫化钼纳米载药体系,并评价其载药量和释药性能。方法:以水热法合成的MoS2纳米片为基底,利用MoS2纳米片上的S空缺位点连接硫辛酸聚乙二醇羧酸,然后通过酰胺反应连接精氨酸-甘氨酸-天冬氨酸(RGD)靶...目的:制备肿瘤微环境响应释放的靶向二硫化钼纳米载药体系,并评价其载药量和释药性能。方法:以水热法合成的MoS2纳米片为基底,利用MoS2纳米片上的S空缺位点连接硫辛酸聚乙二醇羧酸,然后通过酰胺反应连接精氨酸-甘氨酸-天冬氨酸(RGD)靶向分子,再连接上交联剂3-(2-吡啶二硫代)丙酸N-琥珀酰亚胺酯(SPDP),得到药物载体MoS2-PEG-RGD-SPDP(MPRS),MPRS进一步与巯基化的阿霉素(DOX)反应,形成MPRS-DOX纳米载药体系。通过透射电子显微镜(TEM),X-射线光电子能谱仪(XPS)以及纳米粒度电位仪对合成的材料进行表征;利用紫外可见分光光度计测试MPRS的载药性能,采用荧光分光光度计考察MPRS-DOX的释药性能。结果:成功合成MPRS-DOX纳米载药体系,其粒径大小在200nm左右,Zeta电位为+28.2 mV;其载药效率为86.8%,载药量为53.5%。体外释药实验表明,在10 m M谷胱甘肽(GSH)和pH=5.5的条件下DOX释放量最多。结论:成功制备了粒径合适的MPRS-DOX纳米载药体系,MPRS-DOX具有GSH和pH双重响应性,可实现预期的模拟肿瘤微环境内控制释放药物。这种GSH和pH双重响应的纳米载药体系为新一代刺激响应型纳米载药系统的构建提供了新的思路。展开更多
基金Supported by the National Natural Science Foundation of China(No.81873369,81704146,81273868 and 81330088)the Tianjin Municipal Bureau of Labor and Social Security(No.2018015)。
文摘Objective:To investigate whether blood-brain barrier(BBB)served a key role in the edema-relief effect of bloodletting puncture at hand twelve Jing-well points(HTWP)in traumatic brain injury(TBI)and the potential molecular signaling pathways.Methods:Adult male Sprague-Dawley rats were assigned to the shamoperated(sham),TBI,and bloodletting puncture(bloodletting)groups(n=24 per group)using a randomized number table.The TBI model rats were induced by cortical contusion and then bloodletting puncture were performed at HTWP twice a day for 2 days.The neurological function and cerebral edema were evaluated by modified neurological severity score(mNSS),cerebral water content,magnetic resonance imaging and hematoxylin and eosin staining.Cerebral blood flow was measured by laser speckles.The protein levels of aquaporin 4(AQP4),matrix metalloproteinases 9(MMP9)and mitogen-activated protein kinase pathway(MAPK)signaling were detected by immunofluorescence staining and Western blot.Results:Compared with TBI group,bloodletting puncture improved neurological function at 24 and 48 h,alleviated cerebral edema at 48 h,and reduced the permeability of BBB induced by TBI(all P<0.05).The AQP4 and MMP9 which would disrupt the integrity of BBB were downregulated by bloodletting puncture(P<0.05 or P<0.01).In addition,the extracellular signal-regulated kinase(ERK)and p38 signaling pathways were inhibited by bloodletting puncture(P<0.05).Conclusions:Bloodletting puncture at HTWP might play a significant role in protecting BBB through regulating the expressions of MMP9 and AQP4 as well as corresponding regulatory upstream ERK and p38 signaling pathways.Therefore,bloodletting puncture at HTWP may be a promising therapeutic strategy for TBI-induced cerebral edema.
文摘目的:制备肿瘤微环境响应释放的靶向二硫化钼纳米载药体系,并评价其载药量和释药性能。方法:以水热法合成的MoS2纳米片为基底,利用MoS2纳米片上的S空缺位点连接硫辛酸聚乙二醇羧酸,然后通过酰胺反应连接精氨酸-甘氨酸-天冬氨酸(RGD)靶向分子,再连接上交联剂3-(2-吡啶二硫代)丙酸N-琥珀酰亚胺酯(SPDP),得到药物载体MoS2-PEG-RGD-SPDP(MPRS),MPRS进一步与巯基化的阿霉素(DOX)反应,形成MPRS-DOX纳米载药体系。通过透射电子显微镜(TEM),X-射线光电子能谱仪(XPS)以及纳米粒度电位仪对合成的材料进行表征;利用紫外可见分光光度计测试MPRS的载药性能,采用荧光分光光度计考察MPRS-DOX的释药性能。结果:成功合成MPRS-DOX纳米载药体系,其粒径大小在200nm左右,Zeta电位为+28.2 mV;其载药效率为86.8%,载药量为53.5%。体外释药实验表明,在10 m M谷胱甘肽(GSH)和pH=5.5的条件下DOX释放量最多。结论:成功制备了粒径合适的MPRS-DOX纳米载药体系,MPRS-DOX具有GSH和pH双重响应性,可实现预期的模拟肿瘤微环境内控制释放药物。这种GSH和pH双重响应的纳米载药体系为新一代刺激响应型纳米载药系统的构建提供了新的思路。
